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Volume 11

A study guide to allergy and immunology.

For the wheal that won't quit, the swollen lip in the ED, and the patient with one infection too many. Last revised 2026.

4 topics

Allergy & Immunology

Mast Cells · Bradykinin · Immune Deficiency

01

Urticaria

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Clinical & Definitions

Transient, pruritic, erythematous wheals › antihistamines.

Acute: ≤6 weeks. Chronic: >6 weeks.

Triggers

Immunologic: food allergy · viral infection · medication reaction · autoimmune thyroid disease · malignancies (lymphoma).

Physical: pressure · cold · heat · vibration · water · sweating · sunlight.

Other: stress · NSAIDs · hormone therapy · menstruation · exercise · EtOH.

Red Flags · Urticarial Vasculitis

Lesions lasting >24h · non-blanching · painful · scarring · systemic symptoms · purpura / ecchymoses.

Workup › ESR/CRP · skin biopsy.

Chronic Spontaneous Urticaria

Most days of the week, >6 weeks, no clear trigger, ± angioedema. Often associated with autoimmune disease.

Workup: ESR/CRP · TSH / TPO antibody · tryptase · total IgE · biopsy.

Ladder: antihistamine › antihistamine OD › omalizumab (anti-IgE) › cyclosporin.

Type III hypersensitivity
Serum Sickness

Fever · lymphadenopathy · arthralgias following antigen / drug exposure.

Workup › CRP/ESR · C3/C4.

Eosinophilia + periorbital edema
Parasitic Infection

Strongyloidiasis · filariasis · trichinosis.

Mast cell disease
Elevated Tryptase

Tryptase >8 › hereditary or clonal mast cell diseases.

A wheal that scars, hurts, or outlasts the day is not urticaria — it is vasculitis dressed as urticaria.

02

Angioedema

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Clinical

Sudden, temporary edema of lips · face · hands · feet · penis · scrotum · ± abdominal pain.

The first decision is mechanism — mast cell or bradykinin — because the two demand different drugs.

Mast Cell vs Bradykinin

FeatureMast cell-mediatedBradykinin-mediated
Urticaria Present Absent
Other features Bronchospasm · hypotension Isolated edema · GI cramping
Triggers Allergic reaction · NSAIDs · radiocontrast · opioids HAE (FH) · acquired C1 inh deficiency (lymphoma, MGUS, SLE) · ACEi
Workup Clinical C1 esterase inhibitor · C4
Rx epinephrine C1 inhibitor concentrate
α-Gal Syndrome

Delayed anaphylaxis (2–6h after exposure) to mammalian meat. Mediated by IgE against galactose-α-1,3-galactose, often triggered after a tick bite.

Urticaria is the line that divides the two angioedemas. Epinephrine for one, C1 inhibitor for the other — antihistamines for neither alone.

03

Serum Sickness

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Mechanism & Timing

Type III hypersensitivity — immune complex deposition.

Onset: ≤1–2 weeks after exposure.

Clinical & Workup

Features: fever · pruritic rash · polyarthritis · polyarthralgia.

Triggers: rituximab · infliximab · vaccines · venoms · antivenoms.

Labs: ↑ESR/CRP · leukopenia / leukocytosis · AKI · proteinuria.

Serum Sickness–Like Reactions

Triggered by antibiotics · viral infections · vaccines. No immune complexes. No renal involvement. Otherwise similar phenotype.

Management

Avoid the offending agent.

Fever, rash, joints, and a recent biologic — think type III before you think infection.

04

Primary Immunodeficiency Syndromes

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Pattern Recognition

Recurrent sinopulmonary infections, atypical organisms, or unusual sites point to a specific arm of the immune system. The infection pattern is the diagnostic clue.

Infection Signatures

DefectCharacteristic Infections
IgA deficiency S pneumoniae · H influenzae · Giardia
CVID Encapsulated bacteria · Mycoplasma · viruses · Giardia · norovirus · Campylobacter · Ureaplasma
Complement C2–C4 Encapsulated bacteria (CVID-like)
Complement C5–C9 Neisseria gonorrhoeae · N meningitidis
CGD (phagocyte oxidative burst) Aspergillus · S aureus · Burkholderia cepacia · Nocardia
Most common PID
IgA Deficiency

Recurrent sinopulmonary infections (S pneumoniae, H influenzae) · giardiasis.

Rx: S pneumoniae vaccination.

↑ risk: autoimmune disorders (celiac, RA, SLE) · transfusion reactions.

Adult-onset humoral
CVID

Hypogammaglobulinemia · recurrent respiratory infections (S pneumoniae, H influenzae, M pneumoniae, viruses) · infectious diarrhea (Giardia, norovirus, Campylobacter) · urethritis (Mycoplasma, Ureaplasma) · recurrent abscesses.

Dx: low IgG + low IgA/IgM + poor vaccine response (tetanus, pneumococcal).

Rx: IVIG · inactivated vaccines. Avoid live vaccines.

↑ risk: autoimmune disease · IBD · granulomatous disease · bronchiectasis · malignancy.

Complement
Complement Deficiency

Screen: low CH50 (total hemolytic complement).

C2–C4: CVID-like picture · ↑ SLE risk › IVIG.

C5–C9: recurrent Neisseria (N gonorrhoeae, N meningitidis) › meningococcal vaccination.

Phagocyte defect
Chronic Granulomatous Disease

Recurrent cellulitis · skin abscesses · pneumonia · suppurative lymphadenitis.

Classic organisms: Aspergillus · S aureus · Burkholderia cepacia · Nocardia.

Neisseria twice is a complement workup. Catalase-positive abscesses are a phagocyte workup. The bug tells you which arm to test.